Bioequivalence and Bioavailability Forum

Dear Rana,

❝ Does US FDA accepts two groups seperated by time period in parallel design i.e, if study is planned with a sample size of 120 subjects in parallel design, initially study was planned with 60 subjects (group-1) and after one month gap study was planned with 60 subjects (group-2)?.

I don’t know whether I understand you correctly. What do you mean by “planned”? It should be no problem to perform the study in two groups (e.g., for logistic reasons – limited capacity of the clinical site). That would mean planning for 120.
If you already performed the study in 60 subjects, evaluate for BE (which failed), and then want to add another group of 60 you are in trouble. That would be an unplanned sequential design. No way – since the patient’s risk will be inflated. See also FDA’s guidance p9 (“Additional subjects should not be included after data analysis unless the trial was designed from the beginning as a sequential or group sequential design.”) and p13 (“A sequential design, in which the decision to study a second group of subjects is based on the results from the first group, calls for different statistical methods and is outside the scope of this guidance. Those wishing to use a sequential design should consult the appropriate CDER review division.”).

❝ As per USFDA Guidance for Industry, Statistical Approaches to Establishing Bioequivalence, 2001 section VII A, crossover study can be carried out in two or more groups of subjects. Does this criteria can be followed for parallel design studies?

Why not? But only if it was planned as such. Although FDA’s states “If the study is carried out in two or more groups […] at the same site but greatly separated in time (months apart, for example), questions may arise as to whether the results from the several groups should be combined in a single analysis. Such cases should be discussed with the appropriate CDER review division.”
Note: months ≠ one month.

If you want to go for a sequential design you have to wait until someone publishes a statistical framework maintaining te patient’s risk. Currently no way.